Reports from recent years provide compelling evidence about the structure and the existence of functional topography in the cerebellum. However, most of them focused on the motor functions of the cerebellum. Recent studies suggest the involvement of the posterior lobe of the cerebellum in the context of neurodegenerative and cognitive disorders. The pathophysiology of these diseases is not sufficiently understood, and recent studies indicate that it could also affect additional subregions of the cerebellum. Anatomical and clinical studies, combined with neuroimaging, provide new ways of thinking about the organization and functioning of the cerebellum. This review summarizes knowledge about the topography and functions of the cerebellum, and focuses on its anatomical and functional contributions to the development of neurological diseases.

The pathogenesis of Alzheimer\'s disease (AD) remains unclear, but revealing individual differences in functional connectivity (FC) may provide insights and improve diagnostic precision. A hierarchical clustering-based autoencoder with functional connectivity was proposed to categorize 82 AD patients from the Alzheimer\'s Disease Neuroimaging Initiative. Compared to directly performing clustering, using an autoencoder to reduce the dimensionality of the matrix can effectively eliminate noise and redundant information in the data, extract key features, and optimize clustering performance. Subsequently, subtype differences in clinical and graph theoretical metrics were assessed. Results indicate a significant inter-subject heterogeneity in the degree of FC disruption among AD patients. We have identified two neurophysiological subtypes: subtype I exhibits widespread functional impairment across the entire brain, while subtype II shows mild impairment in the Limbic System region. What is worth noting is that we also observed significant differences between subtypes in terms of neurocognitive assessment scores associations with network functionality, and graph theory metrics. Our method can accurately identify different functional disruptions in subtypes of AD, facilitating personalized treatment and early diagnosis, ultimately improving patient outcomes.

UNASSIGNED: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration.
UNASSIGNED: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA.
UNASSIGNED: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r = 0.400, p = 0.005).
UNASSIGNED: Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.

Attention deficit hyperactivity disorder (ADHD) is a common childhood developmental disorder. In recent years, pattern recognition methods have been increasingly applied to neuroimaging studies of ADHD. However, these methods often suffer from limited accuracy and interpretability, impeding their contribution to the identification of ADHD-related biomarkers. To address these limitations, we applied the amplitude of low-frequency fluctuation (ALFF) results for the limbic system and cerebellar network as input data and conducted a binary hypothesis testing framework for ADHD biomarker detection. Our study on the ADHD-200 dataset at multiple sites resulted in an average classification accuracy of 93%, indicating strong discriminative power of the input brain regions between the ADHD and control groups. Moreover, our approach identified critical brain regions, including the thalamus, hippocampal gyrus, and cerebellum Crus 2, as biomarkers. Overall, this investigation uncovered potential ADHD biomarkers in the limbic system and cerebellar network through the use of ALFF realizing highly credible results, which can provide new insights for ADHD diagnosis and treatment.

Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance imaging (MRI) is a powerful tool for investigating whole-brain connectivity patterns; however, systematic assessment of structural connectome organization has rarely been performed. In the present study, we aimed to examine the changes in structural connectivity in patients with episodic migraines using diffusion MRI. First, we computed structural connectivity using diffusion MRI tractography, after which we applied dimensionality reduction techniques to the structural connectivity and generated three low-dimensional eigenvectors. We subsequently calculated the manifold eccentricity, defined as the Euclidean distance between each data point and the center of the data in the manifold space. We then compared the manifold eccentricity between patients with migraines and healthy controls, revealing significant between-group differences in the orbitofrontal cortex, temporal pole, and sensory/motor regions. Between-group differences in subcortico-cortical connectivity further revealed significant changes in the amygdala, accumbens, and caudate nuclei. Finally, supervised machine learning effectively classified patients with migraines and healthy controls using cortical and subcortical structural connectivity features, highlighting the importance of the orbitofrontal and sensory cortices, in addition to the caudate, in distinguishing between the groups. Our findings confirmed that episodic migraine is related to the structural connectome changes in the limbic and sensory systems, suggesting its potential utility as a diagnostic marker for migraine.

OBJECTIVE: The study aimed to identify if clinical features and survival outcomes of insular glioma patients are associated with our classification based on the tumor spread.
METHODS: Our study included 283 consecutive patients diagnosed with histological grade 2 and 3 insular gliomas. A new classification was proposed, and tumors restricted to the paralimbic system were defined as type 1. When tumors invaded the limbic system (referred to as the hippocampus and its surrounding structures in this study) simultaneously, they were defined as type 2. Tumors with additional internal capsule involvement were defined as type 3.
RESULTS: Tumors defined as type 3 had a higher age at diagnosis (p = 0.002) and a higher preoperative volume (p < 0.001). Furthermore, type 3 was more likely to be diagnosed as IDH wild type (p < 0.001), with a higher rate of Ki-67 index (p = 0.015) and a lower rate of gross total resection (p < 0.001). Type 1 had a slower tumor growth rate than type 2 (mean 3.3%/month vs. 19.8%/month; p < 0.001). Multivariate Cox regression analysis revealed the extent of resection (HR 0.259, p = 0.004), IDH status (HR 3.694, p = 0.012), and tumor spread type (HR = 1.874, p = 0.012) as independent predictors of overall survival (OS). Tumor grade (HR 2.609, p = 0.008), the extent of resection (HR 0.488, p = 0.038), IDH status (HR 2.225, p = 0.025), and tumor spread type (HR 1.531, p = 0.038) were significant in predicting progression-free survival (PFS).
CONCLUSIONS: The current study proposes a classification of the insular glioma according to the tumor spread. It indicates that the tumors defined as type 1 have a relatively better nature and biological characteristics, and those defined as type 3 can be more aggressive and refractory. Besides its predictive value for prognosis, the classification has potential value in formulating surgical strategies for patients with insular gliomas.

Aberrant neuronal circuit dynamics are at the core of complex neuropsychiatric disorders, such as schizophrenia (SZ). Clinical assessment of the integrity of neuronal circuits in SZ has consistently described aberrant resting-state gamma oscillatory activity, decreased auditory-evoked gamma responses, and abnormal mismatch responses. We hypothesized that corticothalamic circuit manipulation could recapitulate SZ circuit phenotypes in rodent models. In this study, we optogenetically inhibited the mediodorsal thalamus-to-prefrontal cortex (MDT-to-PFC) or the PFC-to-MDT projection in rats and assessed circuit function through electrophysiological readouts. We found that MDT-PFC perturbation could not recapitulate SZ-linked phenotypes such as broadband gamma disruption, altered evoked oscillatory activity, and diminished mismatch negativity responses. Therefore, the induced functional impairment of the MDT-PFC pathways cannot account for the oscillatory abnormalities described in SZ.

BACKGROUND: Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can effectively alleviate anxiety symptoms. This study aimed to explore the neural mechanisms that drive the therapeutic benefits.
METHODS: We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after a tACS treatment session. tACS was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8 (10-10 EEG convention). With eLORETA, we transformed the scalp signals into the current source density in the cortex. We then assessed the differences between post- and pre-treatment brain maps across multiple spectra (delta to low gamma) with non-parametric statistics.
RESULTS: We observed a trend of heightened power in alpha and reduced power in mid-to-high beta and low gamma, in accord with the EEG markers of anxiolytic effects reported in previous studies. Additionally, we observed a consistent trend of de-synchronization at the stimulating sites across spectra.
CONCLUSIONS: tACS 5-Hz over the right hemisphere demonstrated EEG markers of anxiety reduction. The after-effects of tACS on the brain are intricate and cannot be explained solely by the widely circulated entrainment theory. Rather, our results support the involvement of plasticity mechanisms in the offline effects of tACS.

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

BACKGROUND: One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS).
METHODS: A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 min. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments.
RESULTS: Of the 27 patients, 19 (70.4 %) experienced a reduction in symptom severity >50 %, with an average reduction of BAI 58.5 %. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments.
CONCLUSIONS: The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy.